Institute for Anthropological Research, Zagreb, Croatia.
Centre for Applied Bioanthropology, Institute for Anthropological Research, Zagreb, Croatia.
PLoS One. 2023 Feb 3;18(2):e0279971. doi: 10.1371/journal.pone.0279971. eCollection 2023.
Longevity is a hallmark of successful ageing and a complex trait with a significant genetic component. In this study, 43 single nucleotide polymorphisms (SNPs) were chosen from the literature and genotyped in a Croatian oldest-old sample (85+ years, sample size (N) = 314), in order to determine whether any of these SNPs have a significant effect on reaching the age thresholds for longevity (90+ years, N = 212) and extreme longevity (95+ years, N = 84). The best models were selected for both survival ages using multivariate logistic regression. In the model for reaching age 90, nine SNPs explained 20% of variance for survival to that age, while the 95-year model included five SNPs accounting for 9.3% of variance. The two SNPs that showed the most significant association (p ≤ 0.01) with longevity were TERC rs16847897 and GHRHR rs2267723. Unweighted and weighted Genetic Longevity Scores (uGLS and wGLS) were calculated and their predictive power was tested. All four scores showed significant correlation with age at death (p ≤ 0.01). They also passed the ROC curve test with at least 50% predictive ability, but wGLS90 stood out as the most accurate score, with a 69% chance of accurately predicting survival to the age of 90.
长寿是成功老龄化的标志,是一种具有重要遗传成分的复杂特征。在这项研究中,从文献中选择了 43 个单核苷酸多态性 (SNP),并对克罗地亚最年长的样本(85 岁以上,样本量 (N) = 314)进行了基因分型,以确定这些 SNP 是否对达到长寿(90 岁以上,N = 212)和超长寿(95 岁以上,N = 84)的年龄阈值有显著影响。使用多变量逻辑回归选择了最佳模型,用于两个生存年龄。在达到 90 岁的模型中,有 9 个 SNP 解释了生存到该年龄的 20%的方差,而 95 岁模型包括 5 个 SNP,占 9.3%的方差。与长寿最显著相关(p ≤ 0.01)的两个 SNP 是 TERC rs16847897 和 GHRHR rs2267723。计算了未加权和加权遗传长寿评分 (uGLS 和 wGLS),并测试了它们的预测能力。所有四个评分都与死亡年龄显著相关(p ≤ 0.01)。它们还通过了 ROC 曲线测试,具有至少 50%的预测能力,但 wGLS90 是最准确的评分,有 69%的机会准确预测到 90 岁的生存。